EP1455781B1 - Use of anastrozole for the treatment of post-menopausal women having early breast cancer - Google Patents

Use of anastrozole for the treatment of post-menopausal women having early breast cancer Download PDF

Info

Publication number
EP1455781B1
EP1455781B1 EP02783305A EP02783305A EP1455781B1 EP 1455781 B1 EP1455781 B1 EP 1455781B1 EP 02783305 A EP02783305 A EP 02783305A EP 02783305 A EP02783305 A EP 02783305A EP 1455781 B1 EP1455781 B1 EP 1455781B1
Authority
EP
European Patent Office
Prior art keywords
anastrozole
tamoxifen
breast cancer
patients
treatment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Revoked
Application number
EP02783305A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP1455781A1 (en
Inventor
Paul Plourde
Anthony Rogers
Brent Vose
Michael Dukes
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
AstraZeneca AB
Original Assignee
AstraZeneca AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=9927290&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP1455781(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by AstraZeneca AB filed Critical AstraZeneca AB
Priority to EP08162209A priority Critical patent/EP1997492A1/en
Priority to SI200230746T priority patent/SI1455781T1/sl
Publication of EP1455781A1 publication Critical patent/EP1455781A1/en
Application granted granted Critical
Publication of EP1455781B1 publication Critical patent/EP1455781B1/en
Priority to CY20081101221T priority patent/CY1108462T1/el
Anticipated expiration legal-status Critical
Revoked legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • tamoxifen In post-menopausal women, the anti-oestrogen tamoxifen citrate (NOLVADEXTM) has become accepted as standard first-line treatment of advanced breast cancer. Furthermore, over 34,000 women have taken part in clinical trials of adjuvant tamoxifen following primary surgery.
  • tamoxifen The anti-cancer effect of tamoxifen citrate (hereinafter "tamoxifen”) is related to its ability to compete with oestrogen for binding sites in target tissue such as the breast. In addition, it has a variety of other complicated mechanisms which may mediate its effect, including the induction of transforming growth factor beta from stromal fibroblasts, the reduction in circulating levels of insulin-like growth factor 1, the inhibition of angiogenesis and the induction of apoptosis. Nevertheless, the oestrogen receptor (ER) status of the tumour still remains a powerful predictor of response.
  • ER oestrogen receptor
  • Aromatase inhibitors are a class of compounds that act systematically to inhibit oestrogen synthesis in tissues. These compounds prevent oestrogen biosynthesis by inhibiting the enzyme aromatase, which catalyses the conversion of adrenal androgens (androstenedione and testosterone) to oestrogens (oestrogen and oestradiol). There has therefore been interest in developing these compounds as potential therapies for hormone responsive breast cancer in post-menopausal women.
  • Aminoglutethimide was the first aromatase inhibitor to be approved for treatment of breast cancer and has proven efficacy in post-menopausal women with advanced breast cancer ( Stuart-Harris at al 1984, Acta Oncology 27: 721-728 ). Wider use of the drug has been limited by its lack of specificity, resulting in a requirement for concomitant administration of corticosteroids, and the occurrence of troublesome side effects ( Wells et al 1978, Annals Surgery 187: 475-487 ). Consequently, research has been focused on the development of aromatase inhibitors with greater specificity and a better tolerability profile.
  • ARIMIDEXTM is a non-steroidal aromatase inhibitor which is highly selective, well tolerated and is effective in treating advanced breast cancer ( Buzdar et al 1995, The Breast 4(3): 256-257 Abs 104 ; Jonat et al 1995, European Journal of Cancer 32A(3): 404-412 ; Plourde et al 1995, Journal of Steroid Biochemistry 53:175-179 ). (Further information on the clinical experience with Arimidex can be found in the prescribing information sheet for Arimidex). Anastrozole is described in U.S. patent RE 366717 , which is incorporated by reference herein.
  • Tamoxifen therapy also provides other beneficial effects, which relate to the partial agonistic action of the drug. These include cholesterol-lowering effects ( Love et al 1994, Journal of the National Cancer Institute 86: 1534-1539 ), cardio-protective effects ( McDonald et al 1995, British Medical Journal 311: 977-980 ) and protection against bone loss ( Love et al 1992, New England Journal of Medicine 326: 852-856 ).
  • adverse events are also associated with tamoxifen which can be classified as being either consequences of the anti-oestrogenic action of the drug, e.g. hot flushes, vaginal bleeding or discharge or dryness, or more general effects, e.g. gastro-intestinal intolerance, tumour flare, light headedness, skin rash.
  • One possible combination is a combination of anastrozole and tamoxifen in the light of the proven efficacy of anastrozole in advanced breast cancer, its favourable tolerability and a mechanism of action distinct from tamoxifen.
  • NOLVADEXTM and ARIMIDEXTM are trademarks and are the property of the AstraZeneca group of companies.
  • anastrozole is efficacious and well tolerated in the adjuvant treatment of breast cancer, but even more surprisingly we have found that anastrozole is significantly more effective than tamoxifen for disease-free survival in early breast cancer.
  • anastrozole is significantly more effective than tamoxifen for disease-free survival in early breast cancer.
  • anastrozole or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for the reduction of the rate of recurrence of cancer in a post-menopausal woman having early breast cancer.
  • anastrozole was significantly more effective than tamoxifen in terms of incidence of contralateral breast cancer, thus described herein is the use of anastrozole to reduce the rate of a new contralateral primary tumour in a post-menopausal woman having early breast cancer comprising administering an effective amount of anastrozole, or its pharmaceutically acceptable salt, to a said woman.
  • anastrozole or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for the reduction of the rate of a new contralateral primary tumour in a post-menopausal woman having early breast cancer.
  • Tamoxifen has been approved for use for adjuvant therapy for early breast cancer and thus it could be expected that anastrozole would be synergistic with tamoxifen, depleting the oestrogen receptor of its natural ligand, whilst allowing tamoxifen to exert its beneficial effect via alternative biological mechanisms.
  • anastrozole rather than being more effective than tamoxifen alone, a combination of anastrozole and tamoxifen was only equivalent to tamoxifen and significantly worse than anastrozole alone for adjuvant treatment of early breast cancer.
  • tamoxifen reduces the efficacy of anastrozole for the adjuvant treatment of early breast cancer.
  • anastrozole to reduce the rate of recurrence of cancer in a post-menopausal woman having early breast cancer comprising administering an effective amount of anastrozole or its pharmaceutically acceptable salt to said woman wherein the anastrozole or its pharmaceutically acceptable salt is administered in the substantial absence of tamoxifen.
  • anastrozole or a pharmaceutically acceptable salt thereof substantially in the absence of tamoxifen in the preparation of a medicament for the reduction of the rate of recurrence of cancer in a post-menopausal woman having early breast cancer.
  • phrases 'substantially in the absence of tamoxifen' means that the anastrozole is administered to the patient in the absence of tamoxifen. Patients receiving adjuvant therapy for early breast cancer are likely to have previously received tamoxifen treatment. Thus, this phrase relates to the anastrozole medication rather than the patient being treated.
  • anastrozole to reduce the rate of a new contralateral primary tumour in a post-menopausal woman having early breast cancer comprising administering an effective amount of anastrozole or its pharmaceutically acceptable salt to said woman wherein the anastrozole or its pharmaceutically acceptable salt is administered in the substantial absence of tamoxifen.
  • anastrozole or a pharmaceutically acceptable salt thereof substantially in the absence of tamoxifen in the preparation of a medicament for the reduction of the rate of a new contralateral primary tumour in a post-menopausal woman having early breast cancer.
  • anastrozole, or its pharmaceutically acceptable salt is preferably administered as an adjuvant to surgery, chemotherapy or radiation.
  • Surgery includes lumpectomy, quandrantectomy or mastectomy.
  • the anastrozole or its pharmaceutically acceptable salt is administered to a woman having early breast cancer and the woman is oestrogen receptor positive or progesterone receptor positive, more preferably oestrogen receptor positive, most preferably oestrogen receptor positive and progesterone receptor positive.
  • Anastrozole can be administered at a dose between 0.1 and 10 mg/day, preferably, between 0.5 and 5mg/day, most preferably anastrozole is administered at 1mg/day.
  • anastrozole is administered in the substantial absence of tamoxifen.
  • an anti-oestrogen agent such as arzoxifene, tamoxifen, fulvestrant, lasofoxifene, raloxifene, toremifene, trilostane or TSE 424, preferably in the absence of tamoxifen.
  • Treatment of post-menopausal women is preferred as described above, however, treatment of pre-menopausal women is also contemplated.
  • the administration is carried continuously, for a least one year, preferably for at least two years. Five years continuous treatment is most preferred, although greater than five years treatment is also contemplated.
  • anastrozole may be provided in various formulations such as parentally (e.g. aqueous or oily suspensions) or orally (e.g., tablets, powders, capsules, granules, aqueous or oily suspensions).
  • parentally e.g. aqueous or oily suspensions
  • orally e.g., tablets, powders, capsules, granules, aqueous or oily suspensions.
  • anastrozole is provided in orally available formulations preferably in formulations having from 1 to 10mg anastrozole, most preferably 1mg. In the study described below, 1mg tablets were used.
  • HR is an abbreviation of hazard ratio. Values wherein the hazard ratio is less that 1.00 mean the values are in favour of anastrozole or the combination of anastrozole and tamoxifen as appropriate. Values wherein the hazard ratio is greater than 1.00 means that the values are in favour of tamoxifen.
  • the 'time to events' is the time between the commencement of receiving therapy within the trial and diagnosis of recurrence of breast cancer.
  • Figures 1-3 depict Kaplan-Meier Curves which would be familiar to the skilled man, however, more information can be found in Modelling Survival Data in Medical Research by D.Collett (Published by Chapman & Hall, 1994 ).
  • Figure 1 - Kaplan-Meier Curves of disease-free survival in ITT population The Figure shows 'Time to events (months)' on the X axis and 'Proportion of patients event free (%)' on the Y axis.
  • a trial was designed and conducted to compare the efficacy and safety of tamoxifen and anastrozole alone and with anastrozole and tamoxifen in combination as adjuvant treatment for post-menopausal women with early breast cancer, who have completed their primary therapy.
  • the trial was designed to compare tamoxifen (20mg once daily [od]) and anastrozole (1mg od) and to compare tamoxifen (20mg od) and the combination of anastrozole (1mg od) plus tamoxifen (20mg od) as adjuvant treatment in terms of:
  • the trial was designed as a randomised, double-blind, multicentre trial to compare the efficacy and safety of tamoxifen alone, anastrozole alone and anastrozole in combination with tamoxifen as adjuvant treatment for breast cancer in post-menopausal women.
  • Patients who meet the eligibility criteria were randomised on a 1:1:1 basis into one of three oral treatment schedules to receive one of the following:
  • the double blind trial used both active and placebo anastrozole and tamoxifen tables, in order to maintain blindness to trial therapy.
  • Anastrozole 1 mg and matching anastrozole placebo were supplied as white, film-coated tablets.
  • Tamoxifen 20mg active tablets and matching tamoxifen placebo were supplied as white, round, biconvex tablets.
  • Patients were randomised to receive one of three oral therapy regimens.
  • the daily dose is one tablet of anastrozole (1mg active or placebo) plus one tablet of tamoxifen (20mg active or placebo). Patients were instructed to take their daily dose at approximately the same time each day. At entry to the trial patients received either a 13-week supply or a 26-week supply of trial material.
  • HRT and/or oestrogen creams may be prescribed, and randomised treatment may continue.
  • New breast primaries (either contralateral or ipsilateral) were regarded as disease recurrence events in the statistical analyses of time to recurrence.
  • the primary statistical endpoint of the trial was time to disease recurrence (locoregional or distant recurrence, new primary breast cancer or death from any cause) and safety/tolerability.
  • the secondary statistical endpoints were time to distant recurrence, time to death, the incidence of new breast primaries and the incidence of pre-defined adverse events.
  • two treatment comparisons were made: (1) anastrozole alone compared to tamoxifen alone and (2) tamoxifen alone compared to anastrozole and tamoxifen in combination.
  • the primary analysis strategy included all randomised patients and was performed according to randomised treatment (i.e. 'intention to treat'), with two equally important components:
  • the incidence rates of contralateral breast cancer was formally compared between randomised treatment groups.
  • the primary analysis was based on an intention to treat approach.
  • the incidence rates of the following pre-defined adverse events was formally compared between treatment groups defined by treatment received: hot flushes, nausea and vomiting, asthenia, mood disturbances, musculo-skeletal disorders, vaginal bleeding, vaginal discharge, endometrial cancer, fractures, cataract, venous thromboembolic events, and ischaemic cardiovascular disease.
  • the primary analysis includes all patients who received trial treatment, analysed according to treatment received.
  • a secondary subgroup analysis was also be undertaken, analysed according to trial treatment received, in patients with oestrogen receptor (ER) positive and/or progesterone receptor (PR) positive tumours, patients with ER negative and PR negative tumours, and all other patients remaining safety data was summarised and presented by treatment received.
  • ER oestrogen receptor
  • PR progesterone receptor
  • Results of the study are set forth in Figures 1 , 2 , 3 and 4 and Table 1, 2 and 3.
  • the results relate to a trial consisting of 9,366 patients with a median duration of therapy of 30.7 months with a median follow up of 34.3 months.
  • the total number of first events recorded, i.e. re-emergence of breast cancer, was 1079 of which 766 were in the receptor positive population.
  • the results of the main analysis of the trial indicate a 17% reduction in the rate of recurrence events (which includes locoregional, distant, and contralateral events, as well as deaths) for the patients receiving anastrozole vs. those receiving tamoxifen.
  • the hormone receptor positive (oestrogen receptor positive and/or progesterone receptor positive) patients there was a 22% reduction in recurrence rate for anastrozole vs. tamoxifen patients.
  • Anastrozole was significantly better tolerated (vs. tamoxifen) with respect to endometrial cancer, vaginal bleeding, vaginal discharge, ischemic cerebrovascular events, venous thromboenbolic events, hot flushes and weight gain. Tamoxifen was better tolerated with respect to musculoskeletal disorders and fractures.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Chemical Treatment Of Metals (AREA)
EP02783305A 2001-12-10 2002-12-06 Use of anastrozole for the treatment of post-menopausal women having early breast cancer Revoked EP1455781B1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP08162209A EP1997492A1 (en) 2001-12-10 2002-12-06 Method of treatment
SI200230746T SI1455781T1 (sl) 2001-12-10 2002-12-06 Uporaba anastrozola za zdravljenje postmenopavzalnih žensk z začetnim rakom dojk
CY20081101221T CY1108462T1 (el) 2001-12-10 2008-10-29 Χρηση της αναστροζολης για τη θεραπευτικη αντιμετωπιση μετεμμηνοπαυσιακων γυναικων με καρκινο του μαστου σε πρωιμο σταδιο

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0129457 2001-12-10
GBGB0129457.8A GB0129457D0 (en) 2001-12-10 2001-12-10 Method of treatment
PCT/GB2002/005554 WO2003053438A1 (en) 2001-12-10 2002-12-06 Use of anastrozole for the treatment of post-menopausal women having early breast cancer

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP08162209A Division EP1997492A1 (en) 2001-12-10 2002-12-06 Method of treatment

Publications (2)

Publication Number Publication Date
EP1455781A1 EP1455781A1 (en) 2004-09-15
EP1455781B1 true EP1455781B1 (en) 2008-08-27

Family

ID=9927290

Family Applications (2)

Application Number Title Priority Date Filing Date
EP02783305A Revoked EP1455781B1 (en) 2001-12-10 2002-12-06 Use of anastrozole for the treatment of post-menopausal women having early breast cancer
EP08162209A Withdrawn EP1997492A1 (en) 2001-12-10 2002-12-06 Method of treatment

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP08162209A Withdrawn EP1997492A1 (en) 2001-12-10 2002-12-06 Method of treatment

Country Status (29)

Country Link
US (1) US20050165081A1 (xx)
EP (2) EP1455781B1 (xx)
JP (2) JP5335173B2 (xx)
KR (1) KR100858946B1 (xx)
CN (1) CN100408036C (xx)
AT (1) ATE406160T1 (xx)
AU (1) AU2002347371B2 (xx)
BR (1) BR0214798A (xx)
CA (1) CA2468965C (xx)
CO (1) CO5590926A2 (xx)
CY (1) CY1108462T1 (xx)
DE (1) DE60228616D1 (xx)
DK (1) DK1455781T3 (xx)
ES (1) ES2303811T3 (xx)
GB (1) GB0129457D0 (xx)
HK (1) HK1069335A1 (xx)
HU (1) HUP0402023A3 (xx)
IL (1) IL162150A0 (xx)
IS (1) IS7300A (xx)
MX (1) MXPA04005394A (xx)
NO (1) NO20042912L (xx)
NZ (1) NZ533106A (xx)
PL (1) PL369411A1 (xx)
PT (1) PT1455781E (xx)
RU (1) RU2320339C2 (xx)
SI (1) SI1455781T1 (xx)
UA (1) UA79443C2 (xx)
WO (1) WO2003053438A1 (xx)
ZA (1) ZA200404260B (xx)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0129457D0 (en) * 2001-12-10 2002-01-30 Astrazeneca Ab Method of treatment
US8436029B2 (en) * 2004-03-19 2013-05-07 Transform Pharmaceuticals, Inc. Pharmaceutical forms, and methods of making and using the same
WO2005117864A1 (en) * 2004-05-28 2005-12-15 Astrazeneca Ab Combination product comprising anastrozole and a dual prenyl transferase inhibitor
CN100337625C (zh) * 2004-08-30 2007-09-19 鲁南制药集团股份有限公司 阿那曲唑的分散片剂型
CN1304054C (zh) * 2004-12-29 2007-03-14 山东蓝金生物工程有限公司 一种缓慢释放的抗癌药物组合物
GB0517674D0 (en) * 2005-08-31 2005-10-05 Astrazeneca Ab Formulation
GB0517673D0 (en) * 2005-08-31 2005-10-05 Astrazeneca Ab Formulation
WO2011130381A1 (en) * 2010-04-13 2011-10-20 Estrocept Diagnostics, Inc. Diagnostic assays for breast cancer treatment and progression
US10201549B2 (en) 2013-06-14 2019-02-12 Professional Compounding Centers Of America (Pcca) Testosterone combined with anastrozole injection solutions
CN103450099B (zh) * 2013-09-06 2015-03-25 杭州华东医药集团新药研究院有限公司 阿那曲唑及其一水合物的新晶型、制备和用途
RU2548722C1 (ru) * 2013-12-06 2015-04-20 Федеральное государственное бюджетное учреждение "Национальный исследовательский центр "Курчатовский институт" Противоопухолевое лекарственное средство пролонгированного действия на основе противоопухолевого препарата, ингибитора синтеза эстрогенов - анастрозола
DE102014005513B4 (de) * 2014-04-15 2018-03-15 Sanoxsys Gmbh Mittel zur Prävention und Therapie von Tumorerkrankungen

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8714013D0 (en) * 1987-06-16 1987-07-22 Ici Plc (substituted-aralkyl)heterocyclic compounds
AR034142A1 (es) * 2000-09-08 2004-02-04 Sloan Kettering Inst Cancer Una composicion farmaceutica, metodo para fabricar un medicamento en base a dicha composicion y uso de la composicion
GB0129457D0 (en) * 2001-12-10 2002-01-30 Astrazeneca Ab Method of treatment

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EBCTCG: "Tamoxifen for early breast cancer: an overview of the randomized trials" LANCET, vol. 351, 1998, pages 1415-1467 *
THE ATAC TRIALISTS GROUP: "Results of the ATAC trial after completion of 5 years adjuvant treatment for breast cancer" LANCET, vol. 365, 2005, pages 60-62 *

Also Published As

Publication number Publication date
CA2468965A1 (en) 2003-07-03
RU2004121162A (ru) 2005-05-20
NO20042912L (no) 2004-08-25
DK1455781T3 (da) 2008-11-24
HK1069335A1 (en) 2005-05-20
UA79443C2 (en) 2007-06-25
JP2011016828A (ja) 2011-01-27
ATE406160T1 (de) 2008-09-15
ES2303811T3 (es) 2009-02-01
CO5590926A2 (es) 2005-12-30
NZ533106A (en) 2008-02-29
CN1630519A (zh) 2005-06-22
RU2320339C2 (ru) 2008-03-27
ES2303811T1 (es) 2008-09-01
MXPA04005394A (es) 2005-04-19
DE60228616D1 (de) 2008-10-09
CA2468965C (en) 2011-08-30
IL162150A0 (en) 2005-11-20
JP5335173B2 (ja) 2013-11-06
EP1455781A1 (en) 2004-09-15
US20050165081A1 (en) 2005-07-28
HUP0402023A2 (hu) 2005-01-28
PL369411A1 (en) 2005-04-18
JP2005516021A (ja) 2005-06-02
BR0214798A (pt) 2004-10-19
IS7300A (is) 2004-06-04
AU2002347371A1 (en) 2003-07-09
KR100858946B1 (ko) 2008-09-17
KR20040066886A (ko) 2004-07-27
AU2002347371B2 (en) 2007-05-10
GB0129457D0 (en) 2002-01-30
HUP0402023A3 (en) 2008-08-28
CN100408036C (zh) 2008-08-06
EP1997492A1 (en) 2008-12-03
WO2003053438A1 (en) 2003-07-03
SI1455781T1 (sl) 2008-12-31
PT1455781E (pt) 2008-11-03
CY1108462T1 (el) 2014-04-09
ZA200404260B (en) 2005-10-26

Similar Documents

Publication Publication Date Title
US10034860B2 (en) Estrogen receptor modulator for the treatment of locally advanced or metastatic estrogen receptor positive breast cancer
Paridaens et al. Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer
JP2011016828A (ja) 早期乳癌を有する閉経後の女性の処置のためのアナストロゾールの使用
Goss et al. Aromatase inhibitors for chemoprevention
Harris et al. Aminoglutethimide for the treatment of advanced postmenopausal breast cancer
Campos et al. A comparative study of exemestane versus anastrozole in patients with postmenopausal breast cancer with visceral metastases
JP7376540B2 (ja) リンパ節陽性の初期ホルモン受容体陽性かつヒト上皮成長因子受容体２陰性乳癌の補助治療のための内分泌療法とアベマシクリブとの組み合わせ
Chung et al. The role of aromatase inhibitors in early breast cancer
Neyro et al. Bone protection during breast cancer treatment.
Tariq et al. Hormonal Therapies in Cancers
AU2004281527A1 (en) Breast cancer treatment regimen
Tamaki et al. Aromatase inhibitors for treatment of postmenopausal patients with breast cancer
Bosman No two breast cancers are the same
Gardella et al. Palliative treatment of endometrial cancer type 1 in elderly women with Anastrozole.
Ackland Drug treatment of breast cancer
Dean Hormone treatment for breast cancer
Kishan et al. Low rate of clinician-scored gynecomastia induced by 6 months of combined androgen blockade in a randomized trial: Implications for prophylactic breast irradiation
Armstrong The current status of adjuvant hormonal therapy combined with radiation therapy for localised prostate cancer
Wardley Endocrine Therapy in Breast Cancer Management
Loncaster et al. BREAST ONCOLOGY GUIDELINES
Breul THERAPY OPTIMIZATION TRIAL OF A COMBINATION OF ORAL ESTRAMUSTINE PHOSPHATE (ESTRACYT®) AND ORAL ETOPOSIDE (VEPESID®) IN HORMONE RESISTANT METASTATIC PROSTATE CANCER
Forbes 3.1 Antioestrogen therapies
Dowsett New standards of care in adjuvant endocrine therapy

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20040712

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO

17Q First examination report despatched

Effective date: 20050401

REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1069335

Country of ref document: HK

17Q First examination report despatched

Effective date: 20050401

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

TPAC Observations filed by third parties

Free format text: ORIGINAL CODE: EPIDOSNTIPA

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: GR

Ref legal event code: PP

Ref document number: 20080300012

Country of ref document: GR

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REF Corresponds to:

Ref document number: 60228616

Country of ref document: DE

Date of ref document: 20081009

Kind code of ref document: P

REG Reference to a national code

Ref country code: PT

Ref legal event code: SC4A

Free format text: AVAILABILITY OF NATIONAL TRANSLATION

Effective date: 20081021

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: GR

Ref legal event code: EP

Ref document number: 20080402948

Country of ref document: GR

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

REG Reference to a national code

Ref country code: EE

Ref legal event code: FG4A

Ref document number: E002424

Country of ref document: EE

Effective date: 20081015

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2303811

Country of ref document: ES

Kind code of ref document: T3

REG Reference to a national code

Ref country code: HK

Ref legal event code: GR

Ref document number: 1069335

Country of ref document: HK

PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

PLAX Notice of opposition and request to file observation + time limit sent

Free format text: ORIGINAL CODE: EPIDOSNOBS2

26 Opposition filed

Opponent name: TEVA PHARMACEUTICAL INDUSTRIES LTD.

Effective date: 20090526

Opponent name: HELM AG

Effective date: 20090526

Opponent name: HEXAL AG

Effective date: 20090526

Opponent name: ALFRED E. TIEFENBACHER GMBH & CO. KG

Effective date: 20090526

Opponent name: STADA ARZNEIMITTEL AG

Effective date: 20090526

NLR1 Nl: opposition has been filed with the epo

Opponent name: ALFRED E. TIEFENBACHER GMBH & CO. KG

Opponent name: TEVA PHARMACEUTICAL INDUSTRIES LTD.

Opponent name: HELM AG

Opponent name: HEXAL AG

Opponent name: STADA ARZNEIMITTEL AG

PLAF Information modified related to communication of a notice of opposition and request to file observations + time limit

Free format text: ORIGINAL CODE: EPIDOSCOBS2

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

PLAF Information modified related to communication of a notice of opposition and request to file observations + time limit

Free format text: ORIGINAL CODE: EPIDOSCOBS2

R26 Opposition filed (corrected)

Opponent name: HELM AG

Effective date: 20090526

Opponent name: ALFRED E. TIEFENBACHER GMBH & CO. KG

Effective date: 20090526

Opponent name: STADA ARZNEIMITTEL AG

Effective date: 20090526

Opponent name: HEXAL AG

Effective date: 20090526

Opponent name: TEVA PHARMACEUTICAL INDUSTRIES LTD.

Effective date: 20090526

NLR1 Nl: opposition has been filed with the epo

Opponent name: HELM AG

Opponent name: STADA ARZNEIMITTEL AG

Opponent name: HEXAL AG

Opponent name: ALFRED E. TIEFENBACHER GMBH & CO. KG

Opponent name: TEVA PHARMACEUTICAL INDUSTRIES LTD.

PLBB Reply of patent proprietor to notice(s) of opposition received

Free format text: ORIGINAL CODE: EPIDOSNOBS3

TPAC Observations filed by third parties

Free format text: ORIGINAL CODE: EPIDOSNTIPA

RDAF Communication despatched that patent is revoked

Free format text: ORIGINAL CODE: EPIDOSNREV1

APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO

APBM Appeal reference recorded

Free format text: ORIGINAL CODE: EPIDOSNREFNO

APBP Date of receipt of notice of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA2O

APBQ Date of receipt of statement of grounds of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA3O

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO

R26 Opposition filed (corrected)

Opponent name: TEVA PHARMACEUTICAL INDUSTRIES LTD.

Effective date: 20090526

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: TR

Payment date: 20131129

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DK

Payment date: 20141211

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20141111

Year of fee payment: 13

Ref country code: GR

Payment date: 20141112

Year of fee payment: 13

Ref country code: SK

Payment date: 20141112

Year of fee payment: 13

Ref country code: CZ

Payment date: 20141113

Year of fee payment: 13

Ref country code: FI

Payment date: 20141209

Year of fee payment: 13

Ref country code: LU

Payment date: 20141211

Year of fee payment: 13

Ref country code: SE

Payment date: 20141211

Year of fee payment: 13

Ref country code: DE

Payment date: 20141202

Year of fee payment: 13

Ref country code: MC

Payment date: 20141028

Year of fee payment: 13

Ref country code: EE

Payment date: 20141206

Year of fee payment: 13

Ref country code: CH

Payment date: 20141212

Year of fee payment: 13

Ref country code: GB

Payment date: 20141203

Year of fee payment: 13

Ref country code: BG

Payment date: 20141010

Year of fee payment: 13

Ref country code: IE

Payment date: 20141209

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20141208

Year of fee payment: 13

Ref country code: PT

Payment date: 20141205

Year of fee payment: 13

Ref country code: SI

Payment date: 20141114

Year of fee payment: 13

Ref country code: AT

Payment date: 20141125

Year of fee payment: 13

Ref country code: NL

Payment date: 20141210

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20141126

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CY

Payment date: 20141118

Year of fee payment: 13

REG Reference to a national code

Ref country code: DE

Ref legal event code: R103

Ref document number: 60228616

Country of ref document: DE

Ref country code: DE

Ref legal event code: R064

Ref document number: 60228616

Country of ref document: DE

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20141211

Year of fee payment: 13

APBU Appeal procedure closed

Free format text: ORIGINAL CODE: EPIDOSNNOA9O

RDAG Patent revoked

Free format text: ORIGINAL CODE: 0009271

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: PATENT REVOKED

REG Reference to a national code

Ref country code: CH

Ref legal event code: PLX

REG Reference to a national code

Ref country code: PT

Ref legal event code: MP4A

Effective date: 20151130

27W Patent revoked

Effective date: 20150603

GBPR Gb: patent revoked under art. 102 of the ep convention designating the uk as contracting state

Effective date: 20150603

REG Reference to a national code

Ref country code: EE

Ref legal event code: MF4A

Ref document number: E002424

Country of ref document: EE

Effective date: 20151222

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Free format text: LAPSE BECAUSE OF THE APPLICANT RENOUNCES

Effective date: 20080827

Ref country code: LI

Free format text: LAPSE BECAUSE OF THE APPLICANT RENOUNCES

Effective date: 20080827

REG Reference to a national code

Ref country code: AT

Ref legal event code: MA03

Ref document number: 406160

Country of ref document: AT

Kind code of ref document: T

Effective date: 20150603

REG Reference to a national code

Ref country code: GR

Ref legal event code: NF

Ref document number: 20080300012

Country of ref document: GR

Effective date: 20160321

Ref country code: GR

Ref legal event code: NF

Ref document number: 20080402948

Country of ref document: GR

Effective date: 20160321

REG Reference to a national code

Ref country code: SI

Ref legal event code: KO00

Effective date: 20160829

REG Reference to a national code

Ref country code: SE

Ref legal event code: ECNC